The present invention relates to a measurement apparatus and a measurement method for measuring a specified component in a liquid sample using a biosensor utilizing an enzymatic reaction.
As a measurement method of a variety of components contained in a biosample and the like, measurement methods employing enzymatic reactions and electrochemical reactions in combination have widely been employed. For example, widely used is a biosensor, which converts a chemical substance in a solution into another substance by the catalytic function of an enzyme and measuring the obtained substance by a redox reaction.
As a method for utilizing such a biosensor, it is general to carry out calibration using a calibration liquid immediately before the use and then carrying out measurement. Carrying out calibration makes it possible to obtain stable measurement values independently of unevenness of the quality of biosensors, alteration of the measurement environments, and fluctuation of the capabilities of sensors with the lapse of time, the like
In this case, since the sensitivity of a biosensor has temperature-dependency, measurement error is possibly caused if there is temperature difference between a measurement sample and the calibration liquid. Therefore, a conventional measurement apparatus is so constituted as to comprise a temperature detection means for a measurement sample, a temperature detection means for a calibration liquid, and a temperature correction means and subsequently aim at improving the measurement precision. For example, a urine inspection apparatus equipped with a glucose sensor and an oxygen sensor is disclosed in the Japanese Patent Laid-Open No. 63-1971 and the specification discloses that the temperature correction is carried out for obtaining a correction value at the use time of the apparatus. Further, in the Japanese Patent Laid-Open No. 62-11160 discloses a measurement apparatus employing a fixed enzyme membrane and the specification disclosed that the temperature correction is carried out by measuring the cell temperature at the time of calibration using a standardized liquid and measurement of a sample.
However, in conventional apparatuses described in the foregoing patent specifications, the temperature measurement means are installed in the sensor parts so as to employ methods for carrying out temperature compensation by measuring the temperature of a calibration liquid and a sample brought into contact with the sensors. However, these methods have the following problems.
At first, since a temperature detector is integrated with a sensor that becomes an obstacle to the miniaturization of the measurement apparatus including the sensor.
Secondly, since a temperature detector is integrated with a sensor in the peripheral part of the sensor, in the case of replacing the sensor with a new one owing to the life termination, the temperature detector is required to be replaced simultaneously to result in increase of running cost. In a biosensor using an enzyme, the life of the sensor is relatively short to make it necessary to replace the sensor in a prescribed frequency and it is therefore very important to solve such problems from a viewpoint of lowering the cost.
Thirdly, the temperature measurement of a calibration liquid has sometimes imprecisely been carried out to give a significant error of the sensor measurement value. The sensor is not so capable as to detect the temperature of a calibration liquid immediately after a sensor is brought into contact with the calibration liquid. The detection temperature is fluctuated in a manner that the detection temperature gradually comes closer to the calibration liquid temperature along a curved line determined based on the factors such as the thermal capacity of the sensor itself, the temperature at the point where the sensor is installed, the ambient temperature, the thermal conductivities of the sensor and the materials of the peripheral parts. Consequently, in the case where the contact of the sensor with the calibration liquid is finished before the sensor reaches the calibration liquid temperature, owing to the delay of the detection temperature and the value different from the true temperature is recognized as the calibration liquid temperature and based on the detected value, the temperature correction is carried out to result in measurement error in the value measured by the sensor. Incidentally, regarding such detection delay, description is given in Japanese Patent Laid-Open No. 2-54027 and Japanese Patent Laid-Open No. 2-54028. In these patent specifications, urine measurement apparatuses with the constitution where a sensor is attached to a toilet stool are disclosed and the specifications refer to the problems owing to the delay of the sensor in the detection of urine temperature when the sensor is splashed with urine. The measurement error caused by such delay of the detection of the calibration liquid temperature becomes a significant problem in the case where a biosensor utilizing the enzymatic reactions is employed. That is because the activity of the enzymatic reactions is remarkably changed depending on the temperature.
The present invention has been developed while taking the above described situation into consideration and aims of saving the installation space by miniaturization of the apparatus and improving the measurement precision while suppressing the running cost in a measurement apparatus employing a biosensor.
The present invention provides a measurement apparatus comprising a biosensor for carrying out measurement of a specified component in a liquid sample using an enzymatic reaction, a computation processing part for obtaining the computed value by computing an output signal of the biosensor, and a container for storing a calibration liquid for calibrating the biosensor, wherein the container is equipped with temperature control means for keeping the calibration liquid at a constant temperature.
Also, the present invention provides a measurement apparatus comprising a biosensor for carrying out measurement of a specified component in a liquid sample using an enzymatic reaction, a computation processing part for obtaining the computed value by computing an output signal of the biosensor, and a container for storing a calibration liquid for calibrating the biosensor, wherein the container is equipped with temperature measurement means for measuring the temperature of the calibration liquid and the computation processing part has a function of correcting the computed value depending on the temperature of the calibration liquid measured by the temperature measurement means.
As described in the paragraph of prior arts, in the case of measurement of the temperature of a calibration liquid in the periphery of a sensor, the detection of the calibration liquid temperature is delayed and a measurement error is sometimes caused. That is attributed to that the limitation of the duration during which the temperature detection means for the calibration liquid is brought into contact with the calibration liquid. To such a problem, the measurement apparatus of the present invention employs the following means for measuring the temperature of the calibration liquid in place of the measurement of the temperature in the sensor periphery: (1) installing temperature control means for keeping a calibration liquid at a constant temperature in a container for storing the calibration liquid or (2) installing a temperature measurement means in a container for storing a calibration liquid and measuring the temperature of the calibration liquid by the means and consequently, the problems derived from the error of the measurement of the calibration liquid temperature in the sensor periphery are solved to heighten the precision of the calibration. In the case where a trace amount of a component in a sample is highly precisely measured, for example, in the case of measurement of urine sugar in a concentration as low as 1 to 5 mg/dl as described somewhere later, the measurement error attributed to the above described detection delay of the calibration liquid temperature becomes impossible to be ignored. According to the present invention, such problems can be solved and highly precise calibration can be performed.
Further, the measurement apparatus provided with a temperature control means has advantages that the circuit for temperature correction can be omitted and that the apparatus can further be miniaturized. For example, if the temperature of a sample, a measurement object, is kept as same as the temperature of the calibration liquid kept at a constant temperature, the temperature correction is made unnecessary. Also, if urine is a measurement sample, since the urine temperature immediately after urination from a human body is about 32xc2x0 C., no temperature correction is required in the case where measurement is carried out by installing a sensor in a toilet stool and directly dropping urine to the sensor part or in the case where sampled urine is immediately measured, and therefore the present invention can preferably be employed.
Further, the measurement apparatus of the present invention is not required to install any temperature detection means for a sample and a calibration liquid in the sensor part, the apparatus can be miniaturized. For that, the apparatus can be in a handy size or a portable type measurement apparatus or can be suitable as an apparatus to be installed in a narrow space such as a toilet.
Further, the measurement apparatus of the present invention is not required to install any temperature detection means for a sample and a calibration liquid in the sensor part, the temperature measurement means is not required to be replaced simultaneously with the replacement of a sensor and the running cost can thus be lowered as compared with that of conventional measurement apparatuses. In order to effectively utilize such an advantage, the biosensor of the present invention is preferable to be constructed of an enzyme electrode 5 in a detachable manner.
Further, the present invention provides a measurement method for carrying out measurement of a specified component in a liquid sample employing a biosensor utilizing an enzymatic reaction, wherein the measurement method comprises a step of keeping the temperature of a calibration liquid constant, a step of carrying out calibration by bringing the calibration liquid into contact with the biosensor, and a step of obtaining the concentration measured value of a specified component in a liquid sample by carrying out measurement for the liquid sample at the same temperature as that of the calibration liquid.
According to the method, the temperature correction of the calibration value is made unnecessary and the measurement procedure can be simplified. Consequently, even in the case of use by a general user, the measured value is prevented from becoming incorrect by the operation error in the temperature correction for the calibration liquid. Further, there takes place no delay of detection of the calibration liquid temperature, which has been a problem in a conventional technique for measuring the temperature of the calibration liquid in the sensor periphery, and highly precise calibration can be carried out. Further, since no temperature measurement means is required to be installed in the sensor, the apparatus can be miniaturized and the running cost can be lowered.
Further, the present invention provides a measurement method for carrying out measurement of a specified component in a liquid sample employing a biosensor utilizing an enzymatic reaction, wherein the measurement method comprises a step of measuring the temperature of a calibration liquid constant, a step of obtaining a calibration value corrected depending on the temperature of the calibration liquid after carrying out the calibration by bringing the calibration liquid into contact with the biosensor, and a step of obtaining the concentration measured value of a specified component in a liquid sample by carrying out correction using the calibration value after measuring the concentration value of the specified component in the liquid sample.
According to the method, there takes place no delay of detection of the calibration liquid temperature, which has been a problem in a conventional technique for measuring the temperature of the calibration liquid in the sensor periphery, and highly precise calibration can be carried out. Further, since no temperature measurement means is required to be installed in the sensor, the apparatus can be miniaturized and the running cost can be lowered.
The present invention employs means for measuring the temperature of a calibration liquid by installing a temperature control means for keeping the calibration liquid at a constant temperature in the container storing the calibration liquid or installing a temperature measurement means in a container storing the calibration liquid. Hence, detection delay of the liquid temperature, which has been a problem in a conventional technique, is solved and the calibration precision is increased. Further, since no temperature detection means for a sample or the calibration liquid was required to be installed in the sensor part, the apparatus can be miniaturized and made to be a handy size and a portable measurement apparatus or to be installed in a narrow space such as a toilet. Further, it is not necessary to replace the temperature detector simultaneously at the time when the sensor is replaced and consequently the running cost can be lowered as compared with that of a conventional measurement apparatus.